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. 2021 Aug 16;S0041-1345(21)00550-9.
doi: 10.1016/j.transproceed.2021.08.019. Online ahead of print.

SARS-CoV-2 in Solid Organ Transplant Recipients: A Structured Review of 2020

Affiliations

SARS-CoV-2 in Solid Organ Transplant Recipients: A Structured Review of 2020

Markus Quante et al. Transplant Proc. .

Abstract

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging health systems all over the world. Particularly high-risk groups show considerable mortality rates after infection. In 2020, a huge number of case reports, case series, and consecutively various systematic reviews have been published reporting on morbidity and mortality risk connected with SARS-CoV-2 in solid organ transplant (SOT) recipients. However, this vast array of publications resulted in an increasing complexity of the field, overwhelming even for the expert reader.

Methods: We performed a structured literature review comprising electronic databases, transplant journals, and literature from previous systematic reviews covering the entire year 2020. From 164 included articles, we identified 3451 cases of SARS-CoV-2-infected SOT recipients.

Results: Infections resulted in a hospitalization rate of 84% and 24% intensive care unit admissions in the included patients. Whereas 53.6% of patients were reported to have recovered, cross-sectional overall mortality reported after coronavirus disease 2019 (COVID-19) was at 21.1%. Synoptic data concerning immunosuppressive medication attested to the reduction or withdrawal of antimetabolites (81.9%) and calcineurin inhibitors (48.9%) as a frequent adjustment. In contrast, steroids were reported to be increased in 46.8% of SOT recipients.

Conclusions: COVID-19 in SOT recipients is associated with high morbidity and mortality worldwide. Conforming with current guidelines, modifications of immunosuppressive therapies mostly comprised a reduction or withdrawal of antimetabolites and calcineurin inhibitors, while frequently maintaining or even increasing steroids. Here, we provide an accessible overview to the topic and synoptic estimates of expectable outcomes regarding in-hospital mortality of SOT recipients with COVID-19.

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. 2021 Aug 17;S1465-3249(21)00753-2.
doi: 10.1016/j.jcyt.2021.07.017. Online ahead of print.

Differentiation of immortalized human multi-lineage progenitor to alveolar type 2-like cells: angiotensin-converting enzyme 2 expression and binding of severe acute respiratory syndrome coronavirus 2 spike and spike 1 proteins

Affiliations

Differentiation of immortalized human multi-lineage progenitor to alveolar type 2-like cells: angiotensin-converting enzyme 2 expression and binding of severe acute respiratory syndrome coronavirus 2 spike and spike 1 proteins

Daniel P Collins et al. Cytotherapy. .

Abstract

Along with the nasal epithelium, the lung epithelium is a portal of entry for sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and many other respiratory viruses. In the case of SARS-CoV-2, the virus surface spike proteins bind to the angiotensin-converting enzyme 2 (ACE-2) receptor to facilitate entry into the respiratory epithelium. Alveolar type 2 (AT2) cells are committed respiratory progenitor cells responsible for the integrity and regeneration of the respiratory epithelium and production of respiratory surfactant proteins. AT2 cells express high levels of surface ACE-2 and thus are a leading target for primary infection by SARS-CoV-2. This study describes a method for directly differentiating telomerase reverse transcriptase-immortalized human cord blood-derived multi-lineage progenitor cells (MLPCs) to AT2-like cells for the purpose of generating an in vitro cellular platform for viral studies. Differentiation was confirmed with the acquisition of AT2 and absence of alveolar type 1 (AT1) specific markers by confocal microscopy. Expression of the ACE-2 receptor was confirmed by immunofluorescence antibody staining, quantitative reverse transcription polymerase chain reaction and binding of biotinylated SARS-CoV-2 spike and spike 1 proteins. The binding of biotinylated spike proteins was specifically blocked by unlabeled spike proteins and neutralizing antibodies. Additionally, it was demonstrated that the spike protein was internalized after binding to the surface membrane of the cells. The authors defined the culture conditions that enabled AT2-like cells to be repeatedly passaged and cryopreserved without further differentiation to AT1. The authors' method provides a stable and renewable source of AT2 cells for respiratory viral binding, blocking and uptake studies.

Keywords: ACE-2; AT2; MLPC; differentiation; spike binding.

Conflict of interest statement

Declaration of Competing Interest DPC is the owner of CytoMedical Design Group, LLC, which does not alter the authors’ adherence to Cytotherapy policies on sharing data and materials.

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. 2021 Jul 24;S0301-5629(21)00311-2.
doi: 10.1016/j.ultrasmedbio.2021.07.014. Online ahead of print.

Coronavirus Disease 2019 Phenotypes, Lung Ultrasound, Chest Computed Tomography and Clinical Features in Critically Ill Mechanically Ventilated Patients

Affiliations

Coronavirus Disease 2019 Phenotypes, Lung Ultrasound, Chest Computed Tomography and Clinical Features in Critically Ill Mechanically Ventilated Patients

Davide Orlandi et al. Ultrasound Med Biol. .

Abstract

Chest computed tomography (CT) may provide insights into the pathophysiology of coronavirus disease 2019 (COVID-19), although it is not suitable for a timely bedside dynamic assessment of patients admitted to intensive care unit (ICU); therefore, lung ultrasound (LUS) has been proposed as a complementary diagnostic tool. The aims of this study were to investigate different lungs phenotypes in patients with COVID-19 and to assess the differences in CT and LUS scores between ICU survivors and non-survivors. We also explored the association between CT and LUS, and oxygenation (arterial partial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2]) and clinical parameters. The study included 39 patients with COVID-19. CT scans revealed types 1, 2 and 3 phenotypes in 62%, 28% and 10% of patients, respectively. Among survivors, pattern 1 was prevalent (p < 0.005). Chest CT and LUS scores differed between survivors and non-survivors both at ICU admission and 10 days after and were associated with ICU mortality. Chest CT score was positively correlated with LUS findings at ICU admission (r = 0.953, p < 0.0001) and was inversely correlated with PaO2/FiO2 (r = -0.375, p = 0.019) and C-reactive protein (r = 0.329, p = 0.041). LUS score was inversely correlated with PaO2/FiO2 (r = -0.345, p = 0.031). COVID-19 presents distinct phenotypes with differences between survivors and non-survivors. LUS is a valuable monitoring tool in an ICU setting because it may correlate with CT findings and mortality, although it cannot predict oxygenation changes.

Keywords: COVID-19; CT scan; ICU; LUS; Lung ultrasound; Phenotypes; SARS-CoV-2.

Conflict of interest statement

Declaration of Competing Interest All authors have no conflict of interest to disclose.

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. 2021 Sep 22.
doi: 10.1056/NEJMoa2113017. Online ahead of print.

Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase

Affiliations

Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase

Hana M El Sahly et al. N Engl J Med. .

Abstract

Background: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported.

Methods: We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021.

Results: The trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified.

Conclusions: The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

Supplementary info

Associated data, Grant support
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. 2021 Sep 22.
doi: 10.1056/NEJMoa2106599. Online ahead of print.

Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel

Affiliations

Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel

Tamara Pilishvili et al. N Engl J Med. .

Abstract

Background: The prioritization of U.S. health care personnel for early receipt of messenger RNA (mRNA) vaccines against severe acute respiratory disease coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), allowed for the evaluation of the effectiveness of these new vaccines in a real-world setting.

Methods: We conducted a test-negative case-control study involving health care personnel across 25 U.S. states. Cases were defined on the basis of a positive polymerase-chain-reaction (PCR) or antigen-based test for SARS-CoV-2 and at least one Covid-19-like symptom. Controls were defined on the basis of a negative PCR test for SARS-CoV-2, regardless of symptoms, and were matched to cases according to the week of the test date and site. Using conditional logistic regression with adjustment for age, race and ethnic group, underlying conditions, and exposures to persons with Covid-19, we estimated vaccine effectiveness for partial vaccination (assessed 14 days after receipt of the first dose through 6 days after receipt of the second dose) and complete vaccination (assessed ≥7 days after receipt of the second dose).

Results: The study included 1482 case participants and 3449 control participants. Vaccine effectiveness for partial vaccination was 77.6% (95% confidence interval [CI], 70.9 to 82.7) with the BNT162b2 vaccine (Pfizer-BioNTech) and 88.9% (95% CI, 78.7 to 94.2) with the mRNA-1273 vaccine (Moderna); for complete vaccination, vaccine effectiveness was 88.8% (95% CI, 84.6 to 91.8) and 96.3% (95% CI, 91.3 to 98.4), respectively. Vaccine effectiveness was similar in subgroups defined according to age (<50 years or ≥50 years), race and ethnic group, presence of underlying conditions, and level of patient contact. Estimates of vaccine effectiveness were lower during weeks 9 through 14 than during weeks 3 through 8 after receipt of the second dose, but confidence intervals overlapped widely.

Conclusions: The BNT162b2 and mRNA-1273 vaccines were highly effective under real-world conditions in preventing symptomatic Covid-19 in health care personnel, including those at risk for severe Covid-19 and those in racial and ethnic groups that have been disproportionately affected by the pandemic. (Funded by the Centers for Disease Control and Prevention.).

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. 2021 Sep 22;jiab485.
doi: 10.1093/infdis/jiab485. Online ahead of print.

Quantifying the impact of COVID-19 non-pharmaceutical interventions on influenza transmission in the United States

Affiliations

Quantifying the impact of COVID-19 non-pharmaceutical interventions on influenza transmission in the United States

Yuchen Qi et al. J Infect Dis. .

Abstract

Background: Nonpharmaceutical interventions (NPIs) have been implemented to suppress the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence indicates that NPIs against COVID-19 may also have effects on the transmission of seasonal influenza.

Methods: In this study, we use an absolute humidity-driven susceptible-infectious-recovered-susceptible (SIRS) model to quantify the reduction of influenza incidence and transmission in the US and HHS (the US Department of Health and Human Services) regions after implementation of NPIs in 2020. We investigate the long-term effect of NPIs on influenza incidence by projecting influenza transmission at the national scale over the next five years, using the SIRS model.

Results: We estimate that incidence of influenza A/H1 and B, which circulated in early 2020, was reduced by more than 60% in the US during the first ten weeks following implementation of NPIs. The reduction of influenza transmission exhibits clear geographical variation. After the control measures are relaxed, potential accumulation of susceptibility to influenza infection may lead to a large outbreak, the scale of which may be affected by length of the intervention period and duration of immunity to influenza.

Discussion: Healthcare systems need to prepare for potential influenza patient surges and advocate vaccination and continued precautions.

Keywords: COVID-19; Influenza; Influenza forecasting; Non-pharmaceutical interventions; SARS-CoV-2.

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. 2021 Sep 22;1-12.
doi: 10.1080/07391102.2021.1977181. Online ahead of print.

In silico and in vitro assays reveal potential inhibitors against 3CL pro main protease of SARS-CoV-2

Affiliations

In silico and in vitro assays reveal potential inhibitors against 3CL pro main protease of SARS-CoV-2

Eldhose Iype et al. J Biomol Struct Dyn. .

Abstract

The COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not showing any sign of slowing down even after the ongoing efforts of vaccination. The threats of new strains are concerning, as some of them are more infectious than the original one. A therapeutic against the disease is, therefore, of urgent need. Here, we use the DrugBank database to screen for potential inhibitors against the 3CLpro main protease of SARS-CoV-2. Instead of using the traditional approach of computational screening by docking, we developed a kernel ridge regressor (using a part of the docking data) to predict the binding energy of ligands. We used this model to screen the DrugBank database and shortlist two lead candidates (bromocriptine and avoralstat) for in vitro enzymatic study. Our results show that the 3CLpro enzyme activity in presence of 100 μM concentration of bromocriptine and avoralstat is 9.9% and 15.9%, respectively. Remarkably, bromocriptine exhibited submicromolar IC50 of 130 nM (0.13 μM). Avoralstat showed an IC50 of 2.16 μM. Further, the interactions of both drugs with 3CLpro were analyzed using molecular dynamics simulations of 100 ns. Results indicate that both ligands are stable in the binding pocket of the 3CLpro receptor. In addition, the MM-PBSA analysis revealed that bromocriptine (-29.37 kcal/mol) has a lower binding free energy compared to avoralstat (-6.91 kcal/mol). Further, hydrogen bond analysis also showed that bromocriptine interacts with the two catalytic residues, His41 and Cys145, more frequently than avoralstat.Communicated by Ramaswamy H. Sarma.

Keywords: COVID-19; Drug discovery: SARS-CoV-2; avoralstat; bromocriptine; high throughput screening; kernel regression; machine learning; molecular docking; molecular dynamics.

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. 2021 Sep 22;JVI0143721.
doi: 10.1128/JVI.01437-21. Online ahead of print.

Discovery and evaluation of entry inhibitors for SARS-CoV-2 and its emerging variants

Affiliations

Discovery and evaluation of entry inhibitors for SARS-CoV-2 and its emerging variants

Arpan Acharya et al. J Virol. .

Abstract

The outbreak of SARS-CoV-2 is responsible for the COVID-19 pandemic. Despite unprecedented research and developmental efforts, SARS-CoV-2-specific antivirals are still unavailable for the treatment of COVID-19. In most instances, SARS-CoV-2 infection initiates with the binding of spike glycoprotein to the host cell ACE2 receptor. Utilizing the crystal structure of the ACE2/Spike receptor-binding domain (S-RBD) complex (PDB file 6M0J) in a computer-aided drug design (CADD) approach, we identified and validated 5 potential inhibitors of S-RBD and ACE-2 interaction. Two of the five compounds, MU-UNMC-1 and MU-UNMC-2, blocked the entry of pseudovirus particles expressing SARS-CoV-2 Spike glycoprotein. In live SARS-CoV-2 infection assays, both the compounds showed antiviral activity with IC50 values in the micromolar range (MU-UNMC-1: IC50= 0.67 μM and MU-UNMC-2: IC50= 1.72 μM) in human bronchial epithelial cells. Furthermore, MU-UNMC-1 and MU-UNMC-2 effectively blocked the replication of rapidly transmitting variants of concern: South African variant B.1.351 (IC50= 9.27 μM & 3.00 μM) and Scotland variant B.1.222 (IC50= 2.64 μM & 1.39 μM) respectively. Following these assays, we conducted 'induced-fit (flexible) docking' to understand the binding mode of MU-UNMC-1/MU-UNMC-2 at the S-RBD/ACE2 interface. Our data showed that mutation N501Y (present in B.1.351 variant) alters the binding mode of MU-UNMC-2 such that it is partially exposed to the solvent and has reduced polar contacts. Finally, MU-UNMC-2 displayed high synergy with remdesivir (RDV), the only approved drug for treating hospitalized COVID-19 patients. IMPORTANCE The ongoing coronavirus infectious disease 2019 (COVID-19) pandemic is caused by a novel coronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). More than 207 million people have been infected globally, and 4.3 million have died due to this viral outbreak. While a few vaccines have been deployed, a SARS-CoV-2 specific antiviral for the treatment of COVID-19 is yet to be approved. As the interaction of SARS-CoV-2 spike protein with ACE2 is critical for cellular entry, using a combination of a computer-aided drug design (CADD) approach and cell-based in vitro assays, we report the identification of five potential SARS-CoV-2 entry inhibitors. Out of the five, two compounds (MU-UNMC-1 and MU-UNMC-2) have antiviral activity against ancestral SARS-CoV-2 and emerging variants from South Africa and Scotland. Furthermore, MU-UNMC-2 acts synergistically with remdesivir, suggesting that RDV and MU-UNMC-2 can be developed as a combination therapy to treat COVID-19, infected individuals.

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. 2021 Sep 22;JVI0153721.
doi: 10.1128/JVI.01537-21. Online ahead of print.

Inhibition of autophagy suppresses SARS-CoV-2 replication and ameliorates pneumonia in hACE2 transgenic mice and xenografted human lung tissues

Affiliations

Inhibition of autophagy suppresses SARS-CoV-2 replication and ameliorates pneumonia in hACE2 transgenic mice and xenografted human lung tissues

Chao Shang et al. J Virol. .

Abstract

Autophagy is thought to be involved in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, how SARS-CoV-2 interferes with the autophagic pathway and whether autophagy contributes to virus infection in vivo is unclear. Here, we identified SARS-CoV-2-triggered autophagy in animal models including the long tailed or crab eating macaque (Macaca fascicularis), hACE2 transgenic mice and xenografted human lung tissues. In Vero E6 and Huh-7 cells, SARS-CoV-2 induces autophagosome formation, accompanied by consistent autophagic events, including inhibition of the Akt-mTOR pathway, and activation of the ULK-1-Atg13 and VPS34-VPS15-Beclin1 complexes, but blocks autophagosome-lysosome fusion. Modulation of autophagic elements, including the VPS34 complex and Atg14, but not Atg5, inhibits SARS-CoV-2 replication. Moreover, this study represents the first to demonstrate that the mouse bearing xenografted human lung tissue is a suitable model for SARS-CoV-2 infection and that autophagy inhibition suppresses SARS-CoV-2 replication and ameliorates virus-associated pneumonia in human lung tissues. We also observed a critical role of autophagy in SARS-CoV-2 infection in an hACE2 transgenic mouse model. This study, therefore, gives insights into the mechanisms by which SARS-CoV-2 manipulates autophagosome formation and we suggest that autophagy-inhibiting agents might be useful as therapeutic agents against SARS-CoV-2 infection. IMPORTANCE: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic with limited therapeutics. Insights into the virus-host interactions contributes substantially. The novelty of this report is the use of a new animal model: mice xenografted with human lung tissues. Using a combination of the in vitro and in vivo studies, we have provided experimental evidence that induction of autophagy contributes to SARS-CoV-2 infection and improves our understanding of potential therapeutic targets for SARS-CoV-2.

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. 2021 Sep 22;AEM0144821.
doi: 10.1128/AEM.01448-21. Online ahead of print.

RNA viromics of Southern California wastewater and detection of SARS-CoV-2 single nucleotide variants

Affiliations

RNA viromics of Southern California wastewater and detection of SARS-CoV-2 single nucleotide variants

Jason A Rothman et al. Appl Environ Microbiol. .

Abstract

Municipal wastewater provides an integrated sample of a diversity of human-associated microbes across a sewershed, including viruses. Wastewater-based epidemiology (WBE) is a promising strategy to detect pathogens and may serve as an early-warning system for disease outbreaks. Notably, WBE has garnered substantial interest during the COVID-19 pandemic to track disease burden through analyses of SARS-CoV-2 RNA. Throughout the COVID-19 outbreak, tracking SARS-CoV-2 in wastewater has been an important tool for understanding the spread of the virus. Unlike traditional sequencing of SARS-CoV-2 isolated from clinical samples, which adds testing burden to the healthcare system, in this study, metatranscriptomics was used to sequence virus directly from wastewater. Here, we present a study in which we explored RNA viral diversity through sequencing 94 wastewater influent samples across seven treatment plants (WTPs), collected August 2020 - January 2021, representing approximately 16 million people in Southern California. Enriched viral libraries identified a wide diversity of RNA viruses that differed between WTPs and over time, with detected viruses including coronaviruses, influenza A, and noroviruses. Furthermore, single nucleotide variants (SNVs) of SARS-CoV-2 were identified in wastewater and we measured proportions of overall virus and SNVs across several months. We detected several SNVs that are markers for clinically-important SARS-CoV-2 variants, along with SNVs of unknown function, prevalence, or epidemiological consequence. Our study shows the potential of WBE to detect viruses in wastewater and to track the diversity and spread of viral variants in urban and suburban locations, which may aid public health efforts to monitor disease outbreaks. Importance: Wastewater based epidemiology (WBE) can detect pathogens across sewersheds, which represents the collective waste of human populations. As there is a wide diversity of RNA viruses in wastewater, monitoring the presence of these viruses is useful for public health, industry, and ecological studies. Specific to public health, WBE has proven valuable during the COVID-19 pandemic to track the spread of SARS-CoV-2 without adding burden to healthcare systems. In this study, we used metatranscriptomics and RT-ddPCR to assay RNA viruses across Southern California wastewater from August 2020 - January 2021, representing approximately 16 million people from Los Angeles, Orange, and San Diego counties. We found that SARS-CoV-2 quantification in wastewater correlates well with county-wide COVID-19 case data, and that we can detect SARS-CoV-2 single nucleotide variants through sequencing. Likewise, WTPs harbored different viromes, and we detected other human pathogens such as noroviruses and adenoviruses, furthering our understanding of wastewater viral ecology.

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. 2021 Sep 22.
doi: 10.1021/acs.jproteome.1c00475. Online ahead of print.

Discovery Proteomics for COVID-19: Where We Are Now

Affiliations

Discovery Proteomics for COVID-19: Where We Are Now

Angela McArdle et al. J Proteome Res. .

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the pandemic coronavirus disease 2019 (COVID-19), which has had a devastating impact on society. Here, we summarize proteomic research that has helped elucidate hallmark proteins associated with the disease with respect to both short- and long-term diagnosis and prognosis. Additionally, we review the highly variable humoral response associated with COVID-19 and the increased risk of autoimmunity.

Keywords: COVID-19; SARS-CoV-2; biofluids; biomarkers; mass spectrometry; plasma; proteomics.

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Review
. 2021 Sep 22;1-8.
doi: 10.1007/s10072-021-05616-1. Online ahead of print.

Alzheimer's disease in elderly COVID-19 patients: potential mechanisms and preventive measures

Affiliations
Review

Alzheimer's disease in elderly COVID-19 patients: potential mechanisms and preventive measures

Haili Wang et al. Neurol Sci. .

Abstract

Advanced age correlates with higher morbidity and mortality among patients affected with the novel coronavirus disease 2019 (COVID-19). Because systemic inflammation and neurological symptoms are also common in severe COVID-19 cases, there is concern that COVID-19 may lead to neurodegenerative conditions such as Alzheimer's disease (AD). In this review, we summarize possible mechanisms by which infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, may cause AD in elderly COVID-19 patients and describe preventive measures to mitigate risk. Potential mechanisms include NLRP3 inflammasome activation and IL-1β release, renin-angiotensin system hyperactivation, innate immune activation, oxidative stress, direct viral infection, and direct cytolytic β-cell damage. Anti-inflammatory therapies, including TNF-α inhibitors and nonsteroidal anti-inflammatory drugs, antioxidants such as the vitamin E family, nutritional intervention, physical activity, blood glucose control, and vaccination are proposed as preventive measures to minimize AD risk in COVID-19 patients. Since several risk factors for AD may converge during severe SARS-CoV-2 infection, neurologists should be alert for potential symptoms of AD and actively implement preventive measures in patients presenting with neuropsychiatric symptoms and in high-risk patients such as the elderly.

Keywords: Alzheimer’s disease; COVID-19; Prevention; Renin-angiotensin system; Systemic inflammation.

Conflict of interest statement

The authors report no conflicts of interest in this work.

Supplementary info

Publication types, Grant support
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Review
. 2021 Sep 22;1-16.
doi: 10.1007/s00284-021-02657-9. Online ahead of print.

Molecular Insights into the Crosstalk Between Immune Inflammation Nexus and SARS-CoV-2 Virus

Affiliations
Review

Molecular Insights into the Crosstalk Between Immune Inflammation Nexus and SARS-CoV-2 Virus

Pritha Bose et al. Curr Microbiol. .

Abstract

COVID-19, a type of viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 has challenged the world as global pandemic. It has marked the identification of third generation of extremely pathogenic zoonotic coronaviruses of twenty-first century posing threat to humans and mainly targeting the lower respiratory tract. In this review, we focused on not only the structure and virology of SARS-COV-2 but have discussed in detail the molecular immunopathogenesis of this novel virus highlighting its interaction with immune system and the role of compromised or dysregulated immune response towards disease severity. We attempted to correlate the crosstalk between unregulated inflammatory outcomes with disrupted host immunity which may play a potential role towards fatal acute respiratory distress syndrome that claims to be life-threatening in COVID-19. Exploration and investigation of molecular host-virus interactions will provide a better understanding on the mechanism of fatal COVID-19 infection and also enlighten the escape routes from the same.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Supplementary info

Publication types
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Review
. 2021 Sep 22;1-9.
doi: 10.1007/s00296-021-04998-x. Online ahead of print.

Reactive arthritis after COVID-19: a case-based review

Affiliations
Review

Reactive arthritis after COVID-19: a case-based review

Burhan Fatih Kocyigit et al. Rheumatol Int. .

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 19 (COVID-19) pandemic, which is deeply affecting the whole world. In this new case for the scientific world, scientists are investigating the etiopathogenesis of viral infection-induced damage and have started to focus on the short and long-term immune system effects and alterations after SARS-CoV-2 infection. The case is here reported of a 53-year-old female patient with acute monoarthritis after SARS-CoV-2 infection, who responded adequately to 150 mg/day diclofenac treatment, and the available case reports are comprehensively reviewed. With the focus on arthritis after SARS-CoV2 infection, which emerges as a new pathological condition associated with COVID-19, it was aimed to examine the possible immunological mechanisms of post-COVID-19 arthritis based on the current data on SARS-CoV-2 and the known pathogenetic background of viral arthritis.

Keywords: Acute arthritis; COVID-19; Reactive arthritis; SARS-CoV-2; Viral arthritis.

Conflict of interest statement

The authors have no conflict of interest to declare.

Supplementary info

Publication types
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. 2021 Sep 22;1-15.
doi: 10.1080/07315724.2021.1965503. Online ahead of print.

Immunostimulant and Antidepressant Effect of Natural Compounds in the Management of Covid-19 Symptoms

Affiliations

Immunostimulant and Antidepressant Effect of Natural Compounds in the Management of Covid-19 Symptoms

Alessio Alesci et al. J Am Coll Nutr. .

Abstract

In recent years, the use of natural compounds as adjuvant treatments and alternatives to traditional pharmacological therapies has become increasingly popular. These compounds have a wide range of biological effects, such as: antioxidant, anti-aging, hypocholesterolizing, hypoglycemic, antitumoral, antidepressant, anxiolytic activity, etc. Almost all of these compounds are easily available and are contained in different foods. At the end of 2019 the Coronavirus SARS-CoV-2 appeared in China and quickly spread throughout the world, causing a pandemic. The most common symptoms of this infection are dry cough, fever, dyspnea, and in severe cases bilateral interstitial pneumonia, with consequences that can lead to death. The nations, in trying to prevent the spread of infection, have imposed social distancing and lockdown measures on their citizens. This had a strong psychological-social impact, leading to phobic, anxious and depressive states. Pharmacological therapy could be accompanied by treatment with several natural compounds, such as vitamins, baicalein, zinc and essential oils. These compounds possess marked immunostimulant activity, strengthening the immune response and mitigating interactions between the virus and the host cell. They also have an antidepressant effect, acting on certain neurotransmitters.

Keywords: COVID-19; baicalein; depression; immune system; vitamins; zinc.

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. 2021 Sep 22;8850666211037326.
doi: 10.1177/08850666211037326. Online ahead of print.

Predictive Value of Eosinophil Count on COVID-19 Disease Progression and Outcomes, a Retrospective Study of Leishenshan Hospital in Wuhan, China

Affiliations

Predictive Value of Eosinophil Count on COVID-19 Disease Progression and Outcomes, a Retrospective Study of Leishenshan Hospital in Wuhan, China

Wei Xuan et al. J Intensive Care Med. .

Abstract

Background: The potential protective role of eosinophils in the COVID-19 pandemic has aroused great interest, given their potential virus clearance function and the infection resistance of asthma patients to this coronavirus. However, it is unknown whether eosinophil counts could serve as a predictor of the severity of COVID-19.

Methods: A total of 1004 patients with confirmed COVID-19 who were admitted to Leishenshan Hospital in Wuhan, China, were enrolled in this study, including 905 patients in the general ward and 99 patients in the intensive care unit (ICU). We reviewed their medical data to analyze the association between eosinophils and ICU admission and death.

Results: Of our 1004 patients with COVID-19, low eosinophil counts/ratios were observed in severe cases. After adjusting for confounders that could have affected the outcome, we found that eosinophil counts might not be a predictor of ICU admission. In 99 ICU patients, 58 of whom survived and 41 of whom died, low eosinophil level was an indicator of death in severe COVID-19 patients with a cutoff value of 0.04 × 109/L, which had an area under the curve of 0.665 (95% CI = 1.089-17.839; P = .045) with sensitivity and specificity of 0.569 and 0.7317, respectively.

Conclusion: Our research revealed that a low eosinophil level is a predictor of death in ICU patients rather than a cause of ICU admission.

Keywords: COVID-19; asthma; coronavirus; eosinophil; leukocyte.

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. 2021 Sep 22;3008916211048234.
doi: 10.1177/03008916211048234. Online ahead of print.

How a pediatric neuro-oncology unit was managed in Madrid during the first wave of the COVID-19 pandemic

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How a pediatric neuro-oncology unit was managed in Madrid during the first wave of the COVID-19 pandemic

Rocio Vila et al. Tumori. .

Abstract

Introduction: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, infection prevention measures were enforced at our Pediatric Neuro-Oncology unit.

Methods: A retrospective study analyzing patients booked in this unit during lockdown was performed to describe its performance.

Results: There were 438 consultations for 123 patients (320 on-site/118 telephone). Eight new diagnoses were made, with one significant delay. Only one patient tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delay in imaging testing occurred in 15 patients. Chemotherapy was delayed in one case. There were no delays in radiotherapy.

Conclusions: Measures implemented were effective in minimizing the risk of COVID-19 infection, achieving continuity in diagnoses and treatment, and avoiding delays that could impact survival.

Keywords: COVID-19; SARS-CoV-2; brain tumor; central nervous system; children; pandemic.

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. 2021 Sep 22;e0108221.
doi: 10.1128/Spectrum.01082-21. Online ahead of print.

Serological Testing Reveals the Hidden COVID-19 Burden among Health Care Workers Experiencing a SARS-CoV-2 Nosocomial Outbreak

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